Toward an Asbestos Ban in the United States.

Many developed countries have banned the use of asbestos, but not the United States. There have, however, been multiple efforts in the US to establish strict exposure standards, to limit asbestos use, and to seek compensation through the courts for asbestos-injured workers' In consequence of these efforts, asbestos use has declined dramatically, despite the absence of a legally mandated ban. This manuscript presents a historical review of these efforts.

Experimental asbestos studies in the UK: 1912-1950.

The asbestos industry originated in the UK in the 1870s. By 1898, asbestos had many applications and was reported to be one of the four leading causes of severe occupational disease. In 1912, the UK government sponsored an experimental study that reported that exposure to asbestos produced no more than a modicum of pulmonary fibrosis in guinea pigs. In the 1930s, the newly established Medical Research Council, with assistance from industry, sponsored a study of the effects of exposing animals to asbestos by injection (intratracheal and subcutaneous) and by inhalation in the factory environment. Government reports, publications, and contemporary records obtained by legal discovery have been reviewed in the context of the stage of scientific development and the history of the times. Experimenters were engaged in a learning process during the 1912-1950 period, and their reports of the effects of asbestos were inconsistent. Pathologists who studied the effects of asbestos experimentally, at whole animal, tissue and cellular levels, advanced experimental methodology and mechanistic knowledge. In the hands of public relations experts, however, research was exploited to preserve an industry and perpetuate preventable diseases, a practice that continues to this day.

Contribution of Academician L. M. Shabad in the theory and practice of preventing cancer from exposure to carcinogenic agents (Leningrad period).

The article is devoted to the Leningrad period of activity of Academician Leon Manusovich Shabad, his contribution to the theory and practice of preventing cancer from exposure to carcinogenic agents.

[Asbestos at the time of the First World War]. / [L'amianto al tempo della Grande Guerra].

Between the end of the 19th century and the beginning of the 20th numerous asbestos industries began operations in various parts of the world. At the time of the First World War there is ample evidence of the use of this mineral in shipbuilding, the aircraft industry and in the construction industry. In the years 1912-17 the writer Franz Kafka was co-proprietor of a small asbestos factory in Prague. Some of the writer's novels and journal pages were inspired by this experience. In this way asbestos entered into the history of 20th century European literature. In 1917 asbestos extraction was started at the quarry in Balangero, near Turin, Italy. Risks related to the use of asbestos were known at the beginning of the 20th century and legislation aimed at preventing the harmful effects of the mineral were approved in Italy.

Influences of Dietary and Other Factors on Xenobiotic Metabolism and Carcinogenesis-A Review Article in Memory of Dr. Allan H. Conney (1930-2013).

This article reviews our current understanding on how xenobiotic metabolism and carcinogenesis are influenced by dietary and other factors. A major contributor to this research area was Dr. Allan Conney, and his contributions are highlighted. His studies on the induction of microsomal xenobiotic-metabolizing enzymes led to the characterization of the cytochrome P450 enzymes, which catalyze the metabolism of drugs, endogenous substrates, carcinogens and many other xenobiotics. These processes are influenced by drugs, diet, and other environmental factors. These studies provided the molecular basis for drug-drug, diet-drug, and herb-drug interactions. The elucidation of the metabolic activation of chemicals to their ultimate carcinogenic forms enables us to understand the molecular basis of chemical carcinogenesis. These studies led to many subsequent investigations on dietary approaches for cancer chemoprevention, including blocking of carcinogen activation, enhancing carcinogen detoxification, and influencing oncogenic pathways, which were carried out by Dr. Conney and others. The strengths and potential for practical application of these approaches are assessed herein.

Historical occupational trichloroethylene air concentrations based on inspection measurements from Shanghai, China.

PURPOSE: Trichloroethylene (TCE) is a carcinogen that has been linked to kidney cancer and possibly other cancer sites including non-Hodgkin lymphoma. Its use in China has increased since the early 1990s with China's growing metal, electronic, and telecommunications industries. We examined historical occupational TCE air concentration patterns in a database of TCE inspection measurements collected in Shanghai, China to identify temporal trends and broad contrasts among occupations and industries. METHODS: Using a database of 932 short-term, area TCE air inspection measurements collected in Shanghai worksites from 1968 through 2000 (median year 1986), we developed mixed-effects models to evaluate job-, industry-, and time-specific TCE air concentrations. RESULTS: Models of TCE air concentrations from Shanghai work sites predicted that exposures decreased 5-10% per year between 1968 and 2000. Measurements collected near launderers and dry cleaners had the highest predicted geometric means (GM for 1986 = 150-190 mg m(-3)). The majority (53%) of the measurements were collected in metal treatment jobs. In a model restricted to measurements in metal treatment jobs, predicted GMs for 1986 varied 35-fold across industries, from 11 mg m(-3) in 'other metal products/repair' industries to 390 mg m(-3) in 'ships/aircrafts' industries. CONCLUSIONS: TCE workplace air concentrations appeared to have dropped over time in Shanghai, China between 1968 and 2000. Understanding differences in TCE concentrations across time, occupations, and industries may assist future epidemiologic studies in China.

[Immunological studies at the N.N. Petrov Research Institute of Oncology (100th anniversary of birth of Prof. T.A. Korosteleva)].

Historical essay devoted to the life and work of Professor Tamara Alexandrovna Korosteleva (1913-1991), the former Head of the Laboratory of Oncoimmunology at the N.N. Petrov Research Institute of Oncology, St. Petersburg.

Estimating historic exposures at the European Gaseous Diffusion plants.

This paper describes the methods and results of an occupational exposure assessment covering 30 years of operation of the EURODIF establishment (1978-2008). The exposure assessment includes radiological, physical and chemical hazards, and takes into account of organizational changes at the establishment. Furthermore, it includes efforts to better quantify the levels of exposures using available industrial hygiene and health physics data. In total, 227 workers participated in the assessment of 26 different occupational exposures in 102 general workstations through 1978-2008. Only 7% of exposure levels were rectified by experts for internal consistency reasons. Noise, heat, trichloroethylene and soluble uranium compounds were the most prevalent exposures at the plant although their levels tended to decrease across time. Assessments of occupational exposure to noise based on JEM exposure levels were fairly well correlated with noise measurement data (Spearman's correlation coefficient, ρ=0.43) while JEM-based assessments of uranium exposure were not well correlated with uranium atmospheric measurements. This study demonstrates the importance of non-radiological exposure in the nuclear fuel industry and highlights the difficulties in managing the risks arising from these exposures. Occupational exposures remain difficult to quantify due to the scarcity of reliable monitoring data and the absence of binding occupational exposure limits for some of considered hazards.

[Asbestos in pre-industrial times: from natural wonder to subject of scientific investigation]. / L'amianto in epoca preindustriale: da meraviglia della natura ad oggetto di approfondimento scientifico.

The author proposes a reading of "Concerning incombustible flax or asbestos stone" which was published in 1696 by Giovanni Giustino Ciampini, who was a historian, a man of the church and scientist in Rome. The text, which was originally written in Latin, is an excellent and early description of the need felt by the majority of scientists in Europe at that time for a change in method: that is, to use scientific experiments to explain and control the natural phenomena observed and even perhaps mythologized right from antiquity. In the case of asbestos this was necessary to check the veracity and consistency of a series of recommendations handed down by the earliest authors but also to revive and reinvent the techniques that had largely been lost so as to be able to utilize and develop a substance that it was thought could be of great benefit to society. In the presentation of Ciampini's text an attempt is made to recall and contextualize the earliest knowledge on asbestos and follow its evolution over a long historical period, up to the first half of the nineteenth century. It can thus be seen how asbestos, once considered "a wonder of nature", became a raw material widely used in industrial applications. The most significant steps in this phase of transformation were taken thanks to Italian entrepreneurs and technicians and to the presence of asbestos in the Alpine valleys of Italy.

Gene-environment interactions in the pre-Industrial Era: the cancer of King Ferrante I of Aragon (1431-1494).

King Ferrante I of Aragon, leading figure of the Italian Renaissance, died in 1494. The autopsy of his mummy revealed a tumor infiltrating the small pelvis. We examined the histologic and molecular features of this ancient tumor to investigate its primary origin. Hematoxylin-eosin, Van Gieson, and Alcian Blue staining showed neoplastic cells infiltrating muscular fibers and forming pseudo-glandular lumina disseminated in fibrous stroma with scarce mucus. A strong immunoreactivity of the neoplastic cells was shown for pancytokeratins and proliferating cell nuclear antigen. Molecular fingerprints were investigated by examining K-ras, BRAF, and microsatellite instability in ancient tumor DNA. Sequencing analysis showed G-to-A transition in codon 12 of K-ras. BRAF mutations and microsatellite instability were not observed. Because the presence of K-ras codon 12 mutation could be associated with exposure to chemical carcinogens, possibly present in some food items, paleodietary reconstruction of the King Ferrante I was carried out by carbon (δ(13)C ) and nitrogen (δ(15)N) stable isotopes analysis. δ(13)C and δ(15)N values found in bone collagen of the King were consistent with a massive intake of animal proteins. Overall, our data show that the tumor of Ferrante I was a mucinous adenocarcinoma with molecular fingerprints characteristic of colorectal carcinogenesis linked to K-ras pathway. Paleodietary reconstruction and historical chronicles indicate a strong consumption of meat by the King. The possible abundance of dietary carcinogens, related to meat consumption, could explain the K-ras mutation causing the colorectal tumor that killed Ferrante I more than 5 centuries ago.

[Concerning the crisis of the West German politics of limit values in the 1970s: the transformation of cancer at the workplace from a toxicological into a socioeconomic problem]. / Zur Krise der westdeutschen Grenzwertpolitik in den 1970er Jahren: Die Verwandlung des Berufskrebes von einem toxikologischen in ein sozioökonomisches Problem.

The paper tackles the changes that occurred in the political culture and the episteme of risk in the Federal Republic of Germany in the 1970s. The objects of observation are limit values for hazardous industrial materials, especially for carcinogens. At the forefront of the production of such values in Germany was the German Research Society's Senate Commission for the Examination of Hazardous Industrial Materials. Limit values bring economy, politics, and science together and they mediate different interests. This makes limit values an ideal object of study to bring together changes in different parts of society. In 1972, a new category of limit values for carcinogenic substances is introduced, the so called "Technische Richtkonzentration" (TRK). This category of values does not assume that complete safety can be reached, as do limit values for hazardous industrial materials, so called "Maximale Arbeitsplatzkonzentrationen" (MAK). This means an important rupture in toxicological thinking. Until the 1970s, Paracelsus' dictum about dosage and poison still served as starting point for toxicologists. The innovation of TRK marks an important rupture in the episteme of regulating dangerous matters. Whereas until the 1970s there existed, at least as an ideal, the myth of "no risk" or "zero tolerance" even in the case of carcinogens, since the beginning of the 1970s, certainty is no more guaranteed by epistemically, but by socially robust knowledge. This also means the return of the risk society at the beginning of the 1970s, whereby cancer at the workplace becomes--in the view of the regulatory bodies--out of a medical problem a socioeconomic illness. The paper argues that these changes are connected to a general feeling of disorientation.

["Substances capable of self-reproduction" as cellular targets of chemical carcinogens]. / "Zur Selbstreproduktion befähigt e Substanze" als zelluläire Angriffsorte chemischer Cancerogene.

In the course of studies on chemical carcinogenesis, which included animal experiments with a carcinogenic azo dye and a mathematical analysis of the observed effects, Hermann Druckrey and Karl Küpfmüller showed in 1948 that carcinogens induce heritable changes by targeting cellular "substances capable of self-reproduction". The authors did not discuss the chemical nature of these substances which remained unclear for a long time thereafter. It was not until 1964 that deoxyribonucleic acid (DNA) was recognized, by Peter Brookes and Philip Lawley, as a target for the genotoxic action of chemical carcinogens. In retrospect, the results of Druckrey and Küpfmüller gave an early, indirect and until now not considered hint to an important role of DNA (the "substance") malfunction in the development of cancer, since DNA is the only molecule capable of self-reproduction. The results are now appreciated in light of the scientific knowledge available at the time.

Pathological recognition of diffuse malignant mesothelioma of the pleura: the significance of the historical perspective as regards this signal tumor.

Diffuse malignant mesothelioma (DMM) is a distinctive tumor which provides an uncommon opportunity to observe the gradual appreciation and increasing incidence of a new disease. DMM is a new disease. One cannot comment intelligently about the pathology of sporadic cases that might have occurred before the beginnings of anatomic pathology, but we do know that there were so few cases before 1930 that the very existence of the disease was not accepted in general before 1930 and not accepted by all pathologists even up until 1960. Because DMM is increasing on a worldwide basis and is making its appearance in the developing world, where it has not previously been diagnosed, appreciation of how the disease came to be noticed sheds light on its causation. As a signal tumor for exposure to asbestos, and knowing that all special exposures contribute to the development of the disease, knowledge of its continuing escalation underscores the importance of recognition of previously unimplicated or occult exposures for reasons of public health in both developed and developing countries.

[On the origins of the Druckrey-Küpfmüller Papers (1948-1949): dose-effect relations in carcinogenic substances]. / Zur Entstehungsgeschichte der Druckrey-Küpfmüller- Schriften (1948-1949): Dosis und Wirkung bei krebserzeugenden Stoffen.

Theoretical knowledge about the relationship between drug dosage and tissue response in pharmacology and toxicology in general, and concerning the action of carcinogenic substances in particular, largely dates back to two papers by Hermann Druckrey and Karl Küpfmüller, published in 1948 and 1949, respectively. The definition of cumulative poisons and the first proof of the irreversibility of carcinogenic effects had an extraordinary impact on cancer research. The story of how these papers came to be written is remarkable for several reasons. First, an interdisciplinary approach resulted in a landmark interpretation of data regarding the quantitative analysis of cancer development. Second, an intensive collaboration developed between Druckrey, a cancer researcher, and Küpfmüller, a mathematically adept electrical and communications engineer. Third, during their temporary "full-time co-operation", both researchers were in an allied internment camp. Thus, their fundamental scientific achievement ultimately resulted from the fulfilment of three conditions of innovation, i.e. compatible visions of the co-operating scientists, interdisciplinary links, and chance.